Chemotherapy Yields Long-Term Physical Health Decline in Breast Cancer

Patients with breast cancer who received endocrine therapy alone had improved physical health outcomes compared with those who received chemotherapy.

Breast cancer survivors who received chemotherapy as treatment experienced a long-lasting physical health decline whereas those who received endocrine therapy without chemotherapy did not, according to findings from a large prospective cohort study published in JAMA Network Open.¹

Compared with women who did not have breast cancer, the physical decline within 2 years of diagnosis was greatest in patients who received both chemotherapy and endocrine therapy (β = −3.26; 95% CI, −3.97 to −2.55) followed by patients who received chemotherapy alone (β = −3.13; 95% CI, −4.19 to −2.07) and patients who received endocrine therapy alone (β = −1.12; 95% CI, −1.64 to −0.60).

From 2 to 5 years, the greatest decline was with chemotherapy and endocrine therapy (β = −1.34; 95% CI, −2.07 to −0.61) then chemotherapy (β = −1.20; 95% CI, −2.32 to −0.07) and endocrine therapy (β = −0.40; 95% CI, −0.94 to 0.14); from 5 years on, the greatest decline was with chemotherapy alone (β = −4.09; 95% CI, −5.91 to −2.27) followed by chemotherapy plus endocrine therapy (β = −1.65; 95% CI, −2.85 to −0.46) and endocrine therapy (β = −0.11; 95% CI, −1.07 to 0.85).

“Patients with breast cancer [have] an abundance of long-term and late health effects and are at risk of earlier onset disease and higher incidence of chronic health conditions,” Clara Bodelon, PhD, MS, senior principal scientist of survivor research at the American Cancer Society and lead study author, stated in a press release on the study.² “This [study] is encouraging news for breast cancer survivors. If they do not receive chemotherapy, it is unlikely that they will have long-lasting physical health decline. However, further studies are needed to confirm these results and to better understand the health consequences of these treatments.”

The study analysis included 15,392 women, of whom 2566 were diagnosed with breast cancer and 12,826 were age-matched without cancer between 2006 and 2013 who were between 30 and 65 years with no history of cancer other than nonmelanoma skin cancer. Study surveys began in 2015.

Diagnosis occurred after 2015 in 53.6% (n = 1375) of patients, 82.2% (n = 2109) had hormone receptor–positive tumors, 54.8% (n = 1405) had localized disease, and 23.7% (n = 608) had breast cancer in situ. Of patients with breast cancer, 433 did not receive chemotherapy or endocrine therapy, 1223 received endocrine therapy, 276 received chemotherapy, and 634 received chemotherapy and endocrine therapy.

The median age of patients with and without breast cancer was 54.1 years (IQR, 47.7-60.0) and 54.1 years (IQR, 47.8-59.9), respectively. The majority of patients were White (89.5% and 89.4%), postmenopausal (48.3% and 50.3%), and did not have diabetes (93.8% and 95.1%).

The 2015 and 2018 survey physical health assessments were done with the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health v1.2 instrument. PROMIS measured self-reported physical health, physical function or ability to carry out everyday activities of daily living, fatigue, and pain. The raw scores of these values were converted, using the Global Health scoring manual, to standardized T-scores. The baseline survey assessment was the self-reported physical health-related item.

The majority of patients with breast cancer returned all 3 surveys (n = 2161, 84.2%), fewer returned only the baseline and 2015 surveys (n = 273, 10.6%), and the fewest returned the baseline and 2018 surveys (n = 132, 5.1%).

After 5 years, with higher values indicating poorer outcomes, self-reported physical health was β = 1.02 (95% CI, 0.79-1.33) with endocrine therapy, β = 2.25 (95% CI, 1.38-3.67) with chemotherapy, and β = 1.74 (95% CI, 1.25-2.42) with chemotherapy and endocrine therapy; ability to carry out everyday activities of daily living was β = 1.07 (95% CI, 0.76-1.49), β = 2.49 (95% CI, 1.42-4.23), and β = 1.39 (95% CI, 0.93-2.03), respectively; fatigue was β = 0.99 (95% CI, 0.75-1.29), β = 2.78 (95% CI, 1.68-4.60), and β = 1.33 (95% CI, 0.96-1.85); and pain was β = 1.01 (95% CI, 0.77-1.33), β = 1.94 (95% CI, 1.12-3.33), and β = 1.10 (95% CI, 0.78-1.54).

Regarding physical health, the decline in scores among those who received endocrine therapy was restricted to women receiving aromatase inhibitors.

“The idea is that patients, as well as primary care physicians and the entire cancer care team, are knowledgeable about the long-term consequences [of] the treatments and can make the appropriate decisions for each [patient],” Bodelon stated in an interview with CancerNetwork®.

References

1. Bodelon C, Masters M, Bloodworth DE, et al. Physical health decline after chemotherapy or endocrine therapy in breast cancer survivors. JAMA Netw Open. 2025;8(2):e2462365. doi:10.1001/jamanetworkopen.2024.62365
2. Chemotherapy and endocrine therapy have different long-term effects on physical health decline for breast cancer survivors, new study suggests. News release. American Cancer Society. February 28, 2025. Accessed March 4, 2025. https://tinyurl.com/bddxvtjp